The on-going diversification of IC functionality has led to the miniaturization of many techniques, i.e. has made many techniques available on an IC. Examples of such miniaturization include (medical) laboratory techniques such as analyte analysis of bodily fluid samples and DNA sequencing techniques.
An example of a lab-on-chip device for the monitoring of DNA sequencing is disclosed in US 2010/0137143 A1. This document discloses a CMOS IC in which a plurality of pH-sensitive electrodes, i.e. pH-sensitive gate electrodes of a plurality of ChemFETs or ISFETs is located in the upper metal layer of the metallization stack of the IC. A passivation layer is formed over the metallization stack, with a plurality of silicon dioxide reaction chambers formed on the passivation stack over respective pH-sensitive gate electrodes. Each reaction chamber contains a bead to which a nucleic acid such as a sequencing primer or a self-priming nucleic acid template is covalently bound, with the FETs detecting changes in pH resulting from the release of H+-ions by the hydrolysis of the inorganic pyrophosphate released when a DNA sequence is extended.
The indirect detection of such DNA sequencing by means of monitoring pH changes is particularly promising because it allows for a more facile detection of single extensions to the DNA strand compared to direct detection methods in which capacitive changes due to such extensions are being monitored.
However, the IC disclosed in US 2010/0137143 A1 has a number of notable drawbacks. Firstly, it requires a relatively large number of additional process steps to manufacture, which adds to the cost of the IC. It is for instance well known per se that for extended gate FETs and ISFETs the signal to noise ratio decreases for decreasing surface area of the sensor electrode
The fact that the passivation layer is used as the pH sensitive material on the extended gate electrodes of the field effect transistors (FETs) in the metallization stack is a further concern as it limits the materials that can be used for the passivation layer to pH-sensitive materials and moreover limits the sensitivity of the FETs due to the fact that the passivation layer is required to have a minimum thickness in order to effectively protect the underlying structures of the IC from external influences.